RATIONALE: Studies of rodents suggest that extracellular fluid and cerebrospinal fluid (CSF) serotonin (5-HT) concentrations provide a better index of released 5-HT than the frequently obtained measure of CSF 5-hydroxyindoleacetic acid (5-HIAA). The measurement of cisternal CSF 5-HT levels in the monkey might offer a method of assessing the effects of agents and actions on central 5-HT functioning in primate brain. OBJECTIVE: To address methodological issues related to the determination of monkey cisternal CSF 5-HT and to examine the effects of a selective serotonin reuptake inhibitor (SSRI) on the measure. METHODS: Monkey CSF was obtained by cisternal puncture and 5-HT levels determined by high performance liquid chromatography, after screening for blood contamination. RESULTS: When blood contamination was minimized, a mean (+/-SD) basal concentration of cisternal CSF 5-HT 87+/-36 pg/ml (n=13) was observed. Good longitudinal stability (variances of 16 and 20%) of CSF 5-HT was demonstrated in two monkeys sampled over a 3-month period. A two-fold increase in CSF 5-HT was seen in seven animals treated with the SSRI sertraline (20 mg/kg PO, mean treatment period of 12 days): pre- and post-drug 5-HT concentrations were 85+/-39 and 162+/-53 pg/ml (P=0.0007); in contrast, levels of 5-HIAA decreased from 40.0+/-5.7 to 20.4+/-2.2 ng/ml (P=0.0001). CONCLUSIONS: The measurement of monkey cisternal CSF 5-HT appears to provide a useful index of central 5-HT release. Initial results tend to support a role for increased extracellular 5-HT in the mechanism of action of chronically administered SSRIs.
RATIONALE: Studies of rodents suggest that extracellular fluid and cerebrospinal fluid (CSF) serotonin (5-HT) concentrations provide a better index of released 5-HT than the frequently obtained measure of CSF 5-hydroxyindoleacetic acid (5-HIAA). The measurement of cisternal CSF 5-HT levels in the monkey might offer a method of assessing the effects of agents and actions on central 5-HT functioning in primate brain. OBJECTIVE: To address methodological issues related to the determination of monkey cisternal CSF 5-HT and to examine the effects of a selective serotonin reuptake inhibitor (SSRI) on the measure. METHODS: Monkey CSF was obtained by cisternal puncture and 5-HT levels determined by high performance liquid chromatography, after screening for blood contamination. RESULTS: When blood contamination was minimized, a mean (+/-SD) basal concentration of cisternal CSF 5-HT 87+/-36 pg/ml (n=13) was observed. Good longitudinal stability (variances of 16 and 20%) of CSF 5-HT was demonstrated in two monkeys sampled over a 3-month period. A two-fold increase in CSF 5-HT was seen in seven animals treated with the SSRI sertraline (20 mg/kg PO, mean treatment period of 12 days): pre- and post-drug 5-HT concentrations were 85+/-39 and 162+/-53 pg/ml (P=0.0007); in contrast, levels of 5-HIAA decreased from 40.0+/-5.7 to 20.4+/-2.2 ng/ml (P=0.0001). CONCLUSIONS: The measurement of monkey cisternal CSF 5-HT appears to provide a useful index of central 5-HT release. Initial results tend to support a role for increased extracellular 5-HT in the mechanism of action of chronically administered SSRIs.
Authors: George M Anderson; Christina S Barr; Stephen Lindell; Amy C Durham; Ilya Shifrovich; J Dee Higley Journal: Psychopharmacology (Berl) Date: 2004-09-25 Impact factor: 4.530
Authors: Hannah Weinberg-Wolf; Nicholas A Fagan; George M Anderson; Marios Tringides; Olga Dal Monte; Steve W C Chang Journal: Neuropsychopharmacology Date: 2018-01-30 Impact factor: 7.853
Authors: Y S Singh; S C Altieri; T L Gilman; H M Michael; I D Tomlinson; S J Rosenthal; G M Swain; M A Murphey-Corb; R E Ferrell; A M Andrews Journal: Transl Psychiatry Date: 2012-02-07 Impact factor: 6.222